The activation of B cells is a complex process which is still poorly understood. The overall objective of this research is to evaluate the roles of the interactions of helper-T cells with Ia antigens on the B-cell membrane and surface immunoglobulin with specific antigen in: (1)\the activation of resting B cells; (2)\the replication of B cells; and (3)\their maturation to immunoglobulin synthesis. The activation of resting unprimed and antigen-primed "memory" B cells will be compared to determine what differences, if any, exist in their properties. This project will also serve as a means to evaluate whether all helper-T cells are capable of promoting the activation of a resting (Go) B cell and whether functionally distinct helper cells are involved in thedifferent stages of B-cell stimulation. These studies will be facilitated by the virtual exclusive use of purified populations of resting and activated antigen-binding B cells and clones of antigen-specific B cells. In the latter case, we will employ clones derived from CFU-B, which will serve as activated B-cell clones, and cloned B-cell lymphomas, at least one of which is knownto represent a resting B cell in its activation properties. As helper-T cells, lines and clones of antigen-specific helper cells will be used, and clones of antigen-specific helper cell hybrids will be employed as they are developed. As sources of nonspecific factors, supernatants from the antigen-specific T-cell lines will be utilized, as will supernatants from functionally active T-cell lymphomas that secrete limited numbers of helper factors. These studies should provide information necessary for our understanding the basis of specificity of the immune response and the regulation of functional interactions of lymphocyte subpopulations. (LB)